Prevention of Aortic Valve Fusion

ABSTRACT

Materials and methods related to blood pump systems are described. These can be used in patients to, for example, monitor arterial pressure, measure blood flow, maintain left ventricular pressure within a particular range, avoid left ventricular collapse, prevent fusion of the aortic valve in a subject having a blood pump, and provide a means to wean a patient from a blood pump.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a Continuation of U.S. patent Appln. Ser. No.16/034,129 filed Jul. 12, 2018 (Allowed); which is a Continuation ofU.S. patent Appln. Ser. No. 15/601,781 filed May 22, 2017 (now U.S. Pat.No. 10,046,098); which is a Divisional of U.S. patent Appln. Ser. No.14/022,312 filed Sep. 10, 2013 (now U.S. Pat. No. 9,687,596); which is aContinuation of U.S. patent Appln. Ser. No. 12/394,185 filed Feb. 27,2009 (now U.S. Pat. No. 8,562,507); all of which are incorporated hereinby reference in their entirety for all purposes.

TECHNICAL FIELD

This document relates to blood pumps, and more particularly to materialsand methods for adjusting the speed of a blood pump based on informationregarding the left ventricular and/or arterial pressure such that fusionof the aortic valve is avoided.

BACKGROUND

Blood pumps can be used to provide mechanical assistance to the heart.The left ventricle pushes blood out of the heart, through the aorta, andinto the body, while the right ventricle pushes blood from the body tothe lungs. Since the left ventricle bears the majority of the heart'sload, it often is the first part of the heart to require assistance.Ventricular assistance can be provided by, for example, a pump that isimplanted in the abdomen in parallel with the cardiovascular system. Inmany cases, an inflow conduit is attached to the left ventricle, and anoutflow conduit is attached to the aorta. While some blood can followits normal route out of the ventricle and into the aorta, other bloodcan pass through the pump, receive a boost, and be pushed into the bodyvia the aorta.

BRIEF SUMMARY

The motor speed of a rotary blood pump can directly affect the level ofassistance provided by the pump, and typically requires careful control.Blood pumps generally can respond to changes in demand for blood, sothat when a subject exercises, for example, the speed of the pump can bemade to increase to ensure that the heart provides adequate blood to thebody.

The speed of a blood pump may require balance, however. For example, apump should not run so slowly that blood does not leave the heart, norrun so quickly that it causes suction in the ventricle, which can leadto ventricle collapse. Rotary pumps typically are most effective whenthey run at the upper end of their range, however.

This document is based in part on the development of blood pumps havingone or more sensors positioned on or within the inflow conduit, theoutflow conduit, or both. Such sensors can be used to assess leftventricular blood pressure and/or arterial blood pressure. As describedherein, blood pressure sensed at an inflow conduit can be anapproximation of left ventricular pressure, and blood pressure sensed atan outflow conduit can be an approximation of arterial pressure. Thespeed of a blood pump can be adjusted based on information regarding theleft ventricular and/or arterial pressure such that, for example, leftventricular pressure is maintained at a level that averts ventricularcollapse, weaning of a patient from the pump is facilitated, and fusionof the aortic valve is avoided. In addition, sensors placed at inflowand/or outflow conduits can be used for continuous, periodic, or ondemand monitoring of blood flow and chronic measurement of arterialpressure.

A rotary blood pump produces constant flow, not pulsatile flow. With theabsence or reduction of biologic pulsatile heart function, the patient'sblood flow will convert from a pulsatile to a constant flow. The patientwill not have a pulse, making standard blood pressure monitoring devicesuseless. A pump with a pressure transducer mounted on the outflowconduit provides an accurate determination of the arterial pressure on acontinual or intermittent basis. Establishing accurate arterialmeasurements and transferring that information to an attendingphysician, for example, can greatly simplify patient management and pumpoperation.

In one aspect, this document features a blood pump system comprising ablood pump having an inflow conduit for receiving blood from a leftventricle of a heart and an outflow conduit for returning blood to acirculatory system, and a controller operably connected to the bloodpump, wherein the inflow conduit comprises a first sensor located todetect an inflow conduit pressure that is substantially the same as leftventricular pressure, wherein the sensor is adapted to send a signalregarding the inflow conduit pressure to the controller, wherein theoutflow conduit comprises a second sensor located to detect an outflowconduit pressure that is substantially the same as arterial pressure,wherein the sensor is adapted to send a signal regarding the outflowconduit pressure to the controller, and wherein the controller isadapted to send a signal to the blood pump such that the speed of theblood pump is periodically and transiently adjusted to increase leftventricular pressure relative to arterial pressure. The blood pump cancomprise a motor that moves blood through the blood pump. Adjusting thespeed of the motor can adjust the speed of the blood pump.

In another aspect, this document features a method for preventing aorticvalve fusion in a subject having a blood pump system that bypasses thesubject's aortic valve, the blood pump system comprising a blood pump,wherein the method comprises detecting left ventricular pressure via asensor present at an inflow conduit of the blood pump system, detectingarterial pressure via a sensor present at an outflow conduit of theblood pump system, and periodically and transiently adjusting the speedof the blood pump such that the left ventricular pressure is increasedsufficiently to permit the aortic valve to open. The blood pump cancomprise a motor, wherein adjusting the speed of the motor can adjustthe speed of the blood pump. The periodic and transient blood pump speedadjustment can be held constant for 5 to 10 beats. The periodic andtransient blood pump speed adjustment can permit washing of the aorticvalve sinus. The method can further comprise increasing the speed of theblood pump such that left ventricular pressure is reduced to a previouslevel.

Unless otherwise defined, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention pertains. Although methods and materialssimilar or equivalent to those described herein can be used to practicethe invention, suitable methods and materials are described below. Allpublications, patent applications, patents, and other referencesmentioned herein are incorporated by reference in their entirety. Incase of conflict, the present specification, including definitions, willcontrol. In addition, the materials, methods, and examples areillustrative only and not intended to be limiting.

The details of one or more embodiments of the invention are set forth inthe accompanying drawings and the description below. Other features,objects, and advantages of the invention will be apparent from thedescription and drawings, and from the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a depiction of an embodiment of a blood pump system asdescribed herein.

FIG. 2 is a flow diagram depicting an embodiment of a method formaintaining left ventricular pressure within a particular range.

FIG. 3 is a flow diagram depicting an embodiment of a method formaintaining left ventricular pressure above a threshold level.

FIG. 4 is a flow diagram depicting an embodiment of a method forgradually weaning a subject off a blood pump system.

FIG. 5 is a flow diagram depicting an embodiment of a method forpreventing aortic valve fusion in a subject having a blood pump system.

DETAILED DESCRIPTION

This document provides materials and methods related to regulating thespeed of a blood pump implanted in an individual, as well as materialsand methods for chronically monitoring pressure and/or blood flow in asubject having an implanted blood pump. As depicted in FIG. 1, bloodpump 10 as described herein can include pump housing 50, inflow conduit60, and outflow conduit 70. Inflow conduit 60 can be configured toreceive blood from the heart of a patient (e.g., from the left ventriclefor a pump providing support for the systemic circulation, or from theright ventricle for a pump providing support to the pulmonarycirculation), while outflow conduit 70 can be configured to return bloodto the circulatory system of the patient (e.g., via the aorta for a pumpproviding support for the systemic circulation, or via the pulmonaryartery for a pump providing support for the pulmonary circulation). Inaddition, either inflow conduit 60, outflow conduit 70, or both inflowconduit 60 and outflow conduit 70 can have one or more sensors that canbe configured to measure blood pressure and/or blood flow. In someembodiments, as shown in FIG. 1, for example, sensor 65 can bepositioned on an interior surface of inflow conduit 60, and sensor 75can be positioned on an interior surface of outflow conduit 70. Sensors65 and 75 can be located at any suitable position on conduits 60 and 70(e.g., proximal to pump housing 50 or, as shown in FIG. 1, distal topump housing 50). In some embodiments, a sensor can be within about 1 toabout 2 cm (e.g., within about 0.75, about 1, about 1.25, about 1.5,about 1.75, about 2, or about 2.25 cm) from pump housing 50 and, forexample, prior to any flexible member of blood pump 10. In some cases, asensor can be positioned on the exterior surface of an inflow or outflowconduit (e.g., a flexible inflow or outflow conduit). A sensor can be,for example, a microelectromechanical system (MEMS), or a MEMS typetransducer.

Blood pump 10 can be connected to a subject's circulatory system suchthat blood can flow from the subject's heart (e.g., from the leftventricle), through blood pump 10 via inflow conduit 60 and outflowconduit 70, and back into the subject's circulation (e.g., via theaorta). In some embodiments, sensor 65 can measure blood pressure atinflow conduit 60. Depending on the placement of sensor 65 on inflowconduit 60 (e.g., proximal or distal to pump housing 50), the pressuremeasured at inflow conduit 60 can be an approximation of the bloodpressure within the subject's heart (e.g., can approximate leftventricular pressure if the pump is connected to the left ventricle).Sensor 75 can measure blood pressure at outflow conduit 70. Depending onthe placement of sensor 75 on outflow conduit 70 (e.g., proximal ordistal to pump housing 50), the pressure measured at outflow conduit 70can be an approximation of arterial pressure.

Sensors 65 and 75 can serve a variety of purposes. Information regardingblood pressure and/or blood flow measured by sensor(s) on a blood pumpcan be sent to controller 80, which can be connected to the sensor(s)(e.g., via one or more leads, such as leads 82 and 84) or, as in otherembodiments, via a wireless configuration and electrically transmitted.In some embodiments, a controller can chronically monitor detected bloodpressure. For example, a sensor positioned on an outflow conduit canconstantly, periodically, or on demand send information regardingdetected blood pressure to a controller, allowing for chronic monitoringof arterial pressure since, as mentioned above, blood pressure measuredat an outflow conduit can be an approximation of arterial pressure. Insome embodiments, one or more sensors positioned at an inflow conduit,an outflow conduit, or both can send information regarding detectedpressure to a controller (e.g., via one or more leads, or via wirelesstransmission). The controller, in turn, can send a signal to the pumpsuch that the speed of the pump is adjusted (e.g., increased ordecreased) depending on the blood pressure at the inflow conduit, theoutflow conduit, or both. Such embodiments can allow for controlledweaning from the pump, maintain left ventricular pressure within adesired range, avoid left ventricular collapse, determine blood pumpflow, and prevent aortic valve fusion, for example.

Systems having at least a Sensor at an Inflow Conduit

In some embodiments, a blood pump system as described herein can becontrolled based on information regarding blood pressure or blood flowat an inflow conduit. For example, a blood pump system can include ablood pump having an inflow conduit for receiving blood from a heart(e.g., from the left or right ventricle of a heart) and an outflowconduit for returning blood to the aorta or to the pulmonarycirculation, and a controller operably connected to the blood pump. Theinflow conduit can have a sensor to detect a conduit pressure, which maybe substantially the same as left ventricular pressure if the inflowconduit receives blood from the left ventricle, or which may besubstantially the same as right ventricular pressure if the inflowconduit receives blood from the right ventricle. The sensor can beadapted to send a signal regarding the conduit pressure to thecontroller. If the detected conduit pressure is less than a lowerthreshold level, for example, the controller can send a signal to theblood pump such that the speed of the pump is reduced. The lowerthreshold pressure level can be, for example, about 10 mm Hg to about100 mm Hg (e.g., about 10 mm Hg, about 15 mm Hg, about 20 mm Hg, about25 mm Hg, about 30 mm Hg, about 35 mm Hg, about 40 mm Hg, about 45 mmHg, about 50 mm Hg, about 55 mm Hg, about 60 mm Hg, about 65 mm Hg,about 70 mm Hg, about 75 mm Hg, about 80 mm Hg, about 85 mm Hg, about 90mm Hg, about 95 mm Hg, or about 100 mm Hg), or any value there between.In some cases, if the detected conduit pressure is greater than an upperthreshold level, the controller can send a signal to the blood pump suchthat the speed of the pump is increased. The upper threshold pressurelevel can be, for example, about 10 mm Hg to about 45 mm Hg greater thanthe lower threshold pressure. In some cases, the upper thresholdpressure can be about 55 mm Hg to about 150 mm Hg (e.g., about 55 mm Hg,about 60 mm Hg, about 65 mm Hg, about 70 mm Hg, about 75 mm Hg, about 80mm Hg, about 85 mm Hg, about 90 mm Hg, about 95 mm Hg, about 100 mm Hg,about 110 mm Hg, about 120 mm Hg, about 130 mm Hg, about 140 mm Hg, orabout 150 mm Hg), or any value there between. The controller can beadjusted by a clinician to set the threshold levels, and the thresholdlevels also can be changed as desired.

Such a blood pump system can be useful to, for example, maintain leftventricular pressure within a preselected range while eliminating oravoiding left ventricular collapse. For example, a method can includedetecting left ventricular pressure in a subject having a blood pumpsystem, via a sensor at an inflow conduit of the blood pump, andincreasing, maintaining, or reducing the speed of the blood pump basedon the detected inflow conduit pressure. In order to maintain leftventricular pressure within a particular range, the speed can be reducedif the detected left ventricular pressure is less than a lower thresholdlevel (thus increasing the left ventricular pressure), and the speed canbe increased if the detected left ventricular pressure is greater thanan upper threshold level (thus decreasing the left ventricularpressure). In this manner, left ventricular pressure can be maintainedbetween the selected upper and lower thresholds. A flow diagramdepicting such a method is shown in FIG. 2. Again, a clinician can setthe upper and lower threshold values, depending on the patient, and canprogram the blood pump system accordingly. By maintaining the leftventricular pressure above a particular level (e.g., a lower threshold),one can prevent the pressure within the left ventricle from becomingnegative, thus avoiding left ventricular collapse.

Similarly, a blood pump system can be useful to maintain rightventricular pressure within a preselected range. For example, a bloodpump system for support of the pulmonary circulation can be configuredsuch that the speed of the pump is continually monitored and adjusted(e.g., increased, decreased, or maintained) based on the rightventricular pressure detected via an inflow conduit sensor, such that apositive right ventricular pressure is maintained. To maintain rightventricular pressure within a particular range (e.g., from about 5 mm Hgto about 20 mm Hg), the speed of the pump can be reduced if the detectedright ventricular pressure is less than a lower threshold level (thusincreasing the right ventricular pressure), and the speed can beincreased if the detected right ventricular pressure is greater than anupper threshold level (thus decreasing the right ventricular pressure).Again, a clinician can set the upper and lower threshold values,depending on the patient, and can program the blood pump systemaccordingly.

In some embodiments, the speed of a blood pump can be adjusted basedonly on whether the pressure measured at the inflow conduit is less thana lower threshold (e.g., as depicted in the flow diagram shown in FIG.3). In such embodiments, the speed of the pump can be reduced if thedetected pressure is less than a particular threshold, and can bemaintained or increased if the detected pressure is not less than thethreshold.

Such a blood pump system also can be useful for controlling blood flowin a subject. For example, blood flow in the subject can be detected viathe inflow and outflow conduit sensors. Flow can be determined bymeasuring the pressure drop across the pump relative to the pump speed.The speed of the pump can be increased, maintained, or reduced based onthe detected blood flow. If the detected blood flow is less than a lowerthreshold level, for example, the controller can send a signal to theblood pump such that the speed of the pump is increased. The lowerthreshold pressure level can be, for example, about 1 lpm to about 8lpm, or any value there between. In some cases, if the detected bloodflow is greater than an upper threshold level, the controller can send asignal to the blood pump such that the speed of the pump is reduced ormaintained. The upper threshold pressure level can be, for example, fromabout 2 lpm to about 10 lpm (e.g., about 5 lpm to about 10 lpm), or anyvalue there between.

In some embodiments, a blood pump system can be configured to facilitategradual weaning of a patient from the pump. For example, a blood pumpsystem can include a blood pump with an inflow conduit for receivingblood from a heart (e.g., from the left ventricle of a heart or from theright ventricle of a heart) and an outflow conduit for returning bloodto the circulatory system (e.g., to the aorta or to the pulmonaryartery), and a controller operably connected to the blood pump via, forexample, wires or via wireless transmissions. The inflow conduit canhave a sensor that can detect inflow conduit pressure that can besubstantially the same as left ventricular pressure or right ventricularpressure, depending whether the system is placed to provide support tothe systemic circulation or to the pulmonary circulation. The sensor cansend a signal regarding the inflow conduit pressure to the controller,and the controller can send a signal to the blood pump such that thespeed of the pump is reduced or maintained if the conduit pressure isless than a lower threshold level, or increased or maintained if theconduit pressure is greater than an upper threshold level. Thus, asystem providing support to the systemic circulation can be configuredto continually adjust the speed of the blood pump such that a positivesystolic left ventricular pressure is maintained, and/or leftventricular end diastolic pressure is maintained within acceptablelevels.

For a system providing support to the systemic circulation, for example,the lower threshold level can be from about 10 mm Hg to about 40 mm Hg(e.g., about 10 mm Hg, about 15 mm Hg, about 20 mm Hg, about 25 mm Hg,about 30 mm Hg, about 35 mm Hg, or about 40 mm Hg), or any value therebetween, and the upper threshold level can be about 65 mm Hg to aboutarterial pressure (e.g., about 65 mm Hg, about 70 mm Hg, about 75 mm Hg,about 80 mm Hg, about 85 mm Hg, about 90 mm Hg, or about arterialpressure), or any value there between. For a system providing support tothe pulmonary circulation, for example, the lower threshold level can befrom about 5 mm Hg to about 20 mm Hg, or any value there between, andthe upper threshold level can be from about 20 mm Hg to about 60 mm Hg,or any value there between.

In some embodiments, a blood pump system can include a first blood pumphaving a first inflow conduit for receiving blood from a left ventricleof a heart and a first outflow conduit for returning blood to acirculatory system, a second blood pump having a second inflow conduitfor receiving blood from a right ventricle or right atrium of a heartand a second outflow conduit for returning blood to a pulmonary system;and a controller operably connected to the first and second blood pumps.The first inflow conduit can have a first inflow sensor located todetect a first conduit pressure that is substantially the same as leftventricular pressure, and the first inflow sensor can be adapted to senda signal regarding the first conduit pressure to the controller. Thesecond inflow conduit can have a second inflow sensor located to detecta second conduit pressure that is substantially the same as rightventricular pressure or right atrial pressure, and the second inflowsensor can be adapted to send a signal regarding the second conduitpressure to the controller.

The controller, in turn, can send a signal to the first blood pump suchthat the speed of the first blood pump is reduced if the first conduitpressure is less than a first lower threshold level (e.g., a lower leftventricular systolic threshold level), or is maintained or increased ifthe first conduit pressure is greater than a first upper threshold level(e.g., an upper left ventricular systolic threshold level). The firstlower threshold level can be, for example, from about 10 mm Hg to about100 mm Hg (e.g., 10 mm Hg, 20 mm Hg, 30 mm Hg, 40 mm Hg, 50 mm Hg, 60 mmHg, 70 mm Hg, 80 mm Hg, 90 mm Hg, or 100 mm Hg), or any value therebetween, and the first upper threshold level can be from about 20 mm Hgto about 150 mm Hg (e.g., 20 mm Hg, 30 mm Hg, 40 mm Hg, 50 mm Hg, 60 mmHg, 70 mm Hg, 80 mm Hg, 90 mm Hg, 100 mm Hg, 110 mm Hg, 120 mm Hg, 130mm Hg, 140 mm Hg, or 150 mm Hg), or any value there between. Such asystem can be configured to continually adjust the speed of the firstblood pump such that a positive left ventricular pressure is maintained(e.g., a systolic left ventricular pressure in the range of 5 mm Hg to50 mm Hg, or 10 mm Hg to 40 mm Hg).

The controller also can send a signal to the second blood pump such thatits speed is reduced if the second conduit pressure is less than asecond lower threshold level (e.g., a lower right ventricular systolicthreshold level), or is maintained or increased if the second conduitpressure is greater than a second upper threshold level (e.g., an upperright systolic threshold level). The second lower threshold level can befrom about 5 mm Hg to about 20 mm Hg (e.g., 5 mm Hg, 10 mm Hg, 15 mm Hg,or 20 mm Hg), or any value there between, and the second upper thresholdlevel can be from about 20 mm Hg to about 60 mm Hg (e.g., 20 mm Hg, 30mm Hg, 40 mm Hg, 50 mm Hg, or 60 mm Hg), or any value there between.

Such a blood pump system can be useful to, for example, continuouslyadjust the speed of the blood pump in order to maintain systolic leftventricular pressure within a narrow range, and also to assist inweaning the subject off the system. As the heart of a subject with ablood pump becomes stronger, it will generate more of its own pressure.Decreasing pump speed as the subject's heart becomes stronger canmaintain the subject's overall blood pressure, which results frompressure generated by the heart. In embodiments where the blood pumpsystem is placed to provide support to the systemic circulation, thespeed of the blood pump is determined not by blood flow, but rather bythe changing pressure generated by the left ventricle itself. Inembodiments where the blood pump system is placed to provide support tothe pulmonary circulation, the speed of the blood pump is determined bythe changing pressure generated by the right ventricle.

A method for using such a blood pump system can include detecting leftor right ventricular pressure, or both left and right ventricularpressure, via one or more inflow conduit sensors, and increasing,maintaining, or decreasing the speed of the blood pump based on thedetected ventricular pressure(s). For example, the pump speed can beincreased if the detected inflow conduit pressure is greater than anupper threshold level, and decreased if the detected inflow conduitpressure is less than a lower threshold level. A clinician can set theupper and lower thresholds on the controller, and can adjust thethresholds as desired.

In some embodiments, if the measured inflow conduit pressure is withinthe selected range, a blood pump system as described herein canfacilitate weaning by shutting down for a particular length of time ornumber of heart beats, for example, and then starting up again (e.g., toreturn to the previously set speed). Such systematic reduction in theamount of support that the system provides to a subject can allow forrecovery of the subject's own heart, and can enable subsequent removalof the blood pump from the subject. For example, full cardiac supportmay be accomplished when the maximum amount of blood is pumped out ofthe left ventricle without left ventricular collapse. This can beachieved by maintaining a positive systolic pressure within the leftventricle in a relatively narrow range (e.g., about a 20 mm Hg range),selectable between 0 and arterial pressure, and by continuouslyadjusting the pump speed to maintain this pressure. Partial support canbe obtained when systolic pressure within the left ventricle ismaintained at about arterial pressure level throughout the systoliccardiac cycle. The speed of the pump can be reduced to accomplish thislower level of support.

Methods for weaning a patient from a blood pump can include a step-wisereduction of blood flow through the pump. The heart must rest, however,to allow recovery before it can fully take over the pumping function.This can be accomplished by gradually increasing the amount of time thebiologic heart spends in partial support, while gradually decreasing theamount of time that the blood pump provides support. Initially, partialsupport by the biologic heart can be allowed for a short period of time(e.g., as selected by a clinician), after which the pump speed can beincreased to provide full support for a second length of time. Such analternating low flow, high flow cycle can be repeated any number oftimes and as often as desired, to ensure that arterial pressure does notdecrease appreciably during the times at which the biologic heartprovides partial support. This is important, as a drop in arterialpressure can indicate that the biologic heart is not capable ofproducing sufficient blood flow in response to biologic demand. If adrop in pressure occurs, the motor speed can be automatically increasedto full flow status. If a drop in pressure does not occur, the length oftime in the partial support period can be increased (e.g.,incrementally), provided that arterial pressure remains stable. Partialsupport provided by the biologic heart for increasingly extended periodsof time with adequate arterial pressure and low end diastolic pressurein the left ventricle can indicate cardiac recovery. In contrast, highend diastolic pressure can indicate cardiac failure.

As indicated in FIG. 4, for example, an exemplary method forfacilitating weaning of a subject from a blood pump can include thefollowing steps:

-   -   (1) Adjust the pump motor speed to maintain a selected systolic        left ventricular pressure between arterial pressure and about 20        mm Hg below arterial pressure for a desired number of beats or        length of time (e.g., five minutes);    -   (2) greatly reduce the pump speed for a desired length of time        (e.g., five minutes) and determine how well the heart recovers        (e.g., based on inflow conduit pressure, which can approximate        left ventricular pressure, such as left ventricular end        diastolic pressure);    -   (3) return the pump to its previous level of function between        arterial pressure and about 20 mm Hg less than arterial        pressure;    -   (4) repeat steps (2) and (3) as desired;    -   (5) greatly reduce the pump speed for a longer length of time        (e.g., 20 minutes) and determine how well the heart recovers;    -   (6) return the pump to its previous level of function between        arterial pressure and about 20 mm Hg less than arterial        pressure;    -   (7) repeat steps (5) and (6) as desired, at least until it is        determined that arterial pressure does not decrease appreciably        during step (5), and left ventricular end pressure is maintained        at acceptable levels; and    -   (8) continue as desired, gradually increasing the length of time        for which the pump is turned down, until the subject can be        weaned off the pump entirely. If the end diastolic pressure is        above a threshold level (e.g., 20 mm Hg), the pump motor speed        can be increased.

It is to be noted that the starting point for step (2) (e.g., the timefor which the pump speed is initially reduced) can vary. For example,the blood pump initially can be slowed down for one to five minutes(e.g., for one, two, three, four, or five minutes), and that time thencan be increased in subsequent cycles of the method. Appropriatestarting points can be determined by a clinician, for example.

Another exemplary method for facilitating weaning of a subject from ablood pump providing support to the pulmonary circulation can includethe following steps:

-   -   (1) adjusting the pump motor speed to maintain a selected right        ventricular pressure between about 5 mm Hg and about 20 mm Hg;    -   (2) reducing the pump motor speed for a first selected number of        beats and determining how well the heart recovers;    -   (3) returning the pump to its previous level of function;    -   (4) repeating steps (b) and (c) at least until the heart        recovery is at an acceptable level;    -   (5) reducing the pump motor speed for a second selected number        of beats that is incrementally greater than the first selected        number of beats and determining how well the heart recovers;    -   (6) returning the pump to its previous level of function;    -   (7) repeating steps (5) and (6) at least until the heart        recovery is at an acceptable level; and    -   (8) gradually increasing the number of beats for which the pump        motor speed is reduced, until the subject can be weaned off the        blood pump system.

In some embodiments, blood flow measurements can be used as the controlparameter, rather than pressure measurements. A blood pump can beoperated at full support level, and blood pump flow can be established.Weaning then can be initiated by reducing the pump speed to reduce theflow by about 0.5 lpm to about 1.5 lpm (e.g., about 0.75 lpm, about 1lpm, or about 1.5 lpm). Such a procedure can be carried out in steps,using time periods selected by a clinician, for example. Pump flowtypically is not reduced to a level less than 1.0 lpm for long periodsof time (e.g., 30 minutes). For a blood pump system providing support tothe systemic circulation, arterial pressure can be monitored at eachlevel to ascertain that it has not decreased appreciably or that theleft ventricular end diastolic pressure has not risen appreciably. Inthe event that a pressure reduction does occur, the motor speed can beincreased to a level at which arterial pressure can be maintained. For ablood pump system providing support to the pulmonary circulation,pulmonary artery pressure and/or central venous pressure (CVP) can bemonitored at each level to ascertain that it has not decreasedappreciably or that right ventricular pressure end diastolic pressurehas not risen appreciably. If the end diastolic pressure or the CVPrises above a threshold level (e.g., 10 mm Hg to 20 mm Hg), the methodcan include increasing the pump motor speed.

Systems having at least a Sensor at an Outflow Conduit

In some embodiments, a system as described herein can be used to providedata based on blood pressure and/or flow at an outflow conduit. Forexample, a blood pump system can be used for continuous, periodic, or ondemand monitoring of arterial pressure (i.e., pressure of circulatingblood on the arteries), or monitoring of pulmonary artery pressure,based on the pressure detected at an outflow conduit. In some cases, ablood pump system can include a blood pump having an inflow conduit forreceiving blood from a heart (e.g., from the left ventricle or the rightventricle) and an outflow conduit for returning blood to a circulatorysystem (e.g., via the aorta) or to the pulmonary circulation, and acontroller operably connected to the blood pump, where the outflowconduit has a sensor that can detect outflow conduit pressure. Theoutflow conduit pressure can be substantially the same as arterialpressure when the outflow conduit returns blood to the circulatorysystem via the aorta, for example, or can be substantially the same aspulmonary artery pressure when the outflow conduit returns blood to thepulmonary circulation.

The sensor can detect outflow conduit pressure on a continual basis oron a periodic basis (e.g., every second, every two seconds, every tenseconds, every 30 seconds, every minute, every two minutes, every fiveminutes, every 10 minutes, every hour, or less often). In some cases,the sensor can be configured to detect outflow conduit pressure ondemand from a user or a clinician, for example. The sensor can beadapted to send a signal regarding the outflow conduit pressure to thecontroller and/or to a display. In some embodiments, the display can bepart of the controller.

In some embodiments, the blood pump system can include an alarm adaptedto activate if the conduit pressure drops below a preset level. Such adrop can be indicative of cardiac failure or pump failure. The alarm canprovide any suitable type of signal to alert a user or a clinician ofthe pressure drop (e.g., an auditory signal, a visual signal, or avibrational signal).

A blood pump system as provided herein can be used in methods formonitoring arterial or pulmonary artery pressure in a subject. Forexample, a method can include using a sensor located in an outflowconduit of a blood pump system to detect arterial pressure in a subjecton a repeated basis, and outputting the detected arterial pressure fordisplay. In another example, a method can include using a sensor locatedin an outflow conduit of a blood pump system to detect pulmonary arterypressure in a subject on a repeated basis, and outputting the detectedpulmonary artery pressure for display. The sensor can detect conduitpressure on a continual basis or on a periodic basis (e.g., everysecond, every two seconds, every ten seconds, every 30 seconds, everyminute, every two minutes, every five minutes, every 10 minutes, everyhour, or less often), for example. In some cases, the sensor can beconfigured to detect outflow conduit pressure on demand from a subject(e.g., a user or a clinician).

A method also can include transmitting data regarding detected arterialor pulmonary artery pressure to a controller, where the controller canformat the data for display. A controller also may process arterial orpulmonary artery pressure data to account for any difference betweenpressure in the outflow conduit and actual arterial or pulmonary arterypressure. For example, a controller can adjust conduit pressure by aadding or subtracting pre-determined amount. Further, in some cases, thedetected (or calculated) arterial or pulmonary artery pressure can bedisplayed in response to an action from a user, e.g., via a controlleror via a display operably connected to a controller.

Systems having Sensors at both an Inflow Conduit and at an OutflowConduit

In some embodiments, a blood pump system can be controlled based oninformation about blood pressure and/or blood flow at both an inflowconduit and an outflow conduit. For example, a blood pump system caninclude a blood pump having an inflow conduit for receiving blood from aheart (e.g., a left ventricle) and an outflow conduit for returningblood to a circulatory system (e.g., via the aorta), and a controlleroperably connected to the blood pump, wherein the inflow conduit has afirst sensor for detecting an inflow conduit pressure that issubstantially the same as left ventricular pressure, and wherein theoutflow conduit has a second sensor for detecting an outflow conduitpressure that is substantially the same as arterial pressure. The firstsensor can be adapted to send a signal regarding the inflow conduitpressure to the controller, and the second sensor can be adapted to senda signal regarding the outflow conduit pressure to the controller.

In some embodiments, the controller can be adapted to send a signal tothe blood pump such that the speed of the blood pump (e.g., the speed ofa motor in the blood pump) is periodically and transiently adjusted(e.g., reduced) so that left ventricular pressure increases. Suchembodiments can be useful, for example, in subjects having blood pumpsystems that bypass the aortic valve, such that the aortic valve doesnot regularly open and close. Increasing left ventricular pressure byreducing pump speed (and thus reducing the flow of blood through thepump) can force the heart to pump blood through the aortic valve, thusforcing the aortic valve to open and reducing the likelihood that thevalve will fuse shut while the pump is in use within the subject. It isnoted that the left ventricular pressure does not necessarily need toexceed the arterial pressure in order for the aortic valve to open,since the valve typically can open if the left ventricular pressure isequal to the arterial pressure. In some cases, the speed of the pumponly needs to be reduced such that left ventricular pressure andarterial pressure are substantially equal, although in some embodimentsthe speed can be reduced such that left ventricular pressure exceedsarterial pressure. Without being bound by a particular mechanism, leftventricular pressure can equal or exceed arterial pressure duringsystole, such that the aortic valve opens when the left ventriclecontracts.

This document also provides a method for preventing aortic valve fusionin a subject having a blood pump as described herein. The method caninclude detecting left ventricular pressure via a sensor present at aninflow conduit of the blood pump, detecting arterial pressure via asensor present at an outflow conduit of the blood pump, and periodicallyand transiently adjusting (e.g., reducing) the speed of the blood pump(e.g., via the blood pump motor) to such an extent that left ventricularpressure is increased relative to arterial pressure, thereby permittingthe aortic valve to open. The pump speed can be adjusted based on timeor based on heart beats, for example. For example, pump speed can bedecreased for a particular length of time (e.g., 5 to 30 seconds) atparticular intervals of time (e.g., every 5 to 20 minutes), or can bedecreased for a particular number of heart beats (e.g., 5 to 30 beats)at particular intervals (e.g., every 300 to 1200 beats). In some cases,the reduced pump speed can occur over a length of time sufficient topermit washing of the aortic valve sinus. At the end of each cycle, thepump speed can be increased (e.g., to return to a previously set level),so that left ventricular pressure decreases relative to arterialpressure. A flow diagram showing an example of such a method ispresented in FIG. 5.

In some embodiments, a blood pump system having sensors at both aninflow conduit and an outflow conduit can be used as a blood flow meter.Such systems can be used for continuous, periodic, or on demandmonitoring of blood flow through the pump. A blood pump system caninclude, for example, a blood pump with an inflow conduit for receivingblood from the heart (e.g., from the left ventricle) and an outflowconduit for returning blood to the circulatory system (e.g., via theaorta), and a controller operably connected to the blood pump, whereinthe inflow conduit has a first sensor for detecting an inflow conduitpressure and the outflow conduit has a second sensor for detecting anoutflow conduit pressure. The inflow conduit pressure can besubstantially the same as left ventricular pressure, and the firstsensor can be adapted to send a signal regarding the inflow conduitpressure to the controller. Similarly, the outflow conduit pressure canbe substantially the same as arterial pressure, and the sensor can beadapted to send a signal regarding the outflow conduit pressure to thecontroller. The controller, in turn, can be adapted to calculate bloodflow through the pump based on the inflow conduit pressure and theoutflow conduit pressure. Blood flow calculation can be based, forexample, on blood pump motor speed and on pressure changes within theblood pump (e.g., the pressure drop across the pump). In some cases, thecontroller can be adapted to output information regarding calculatedblood flow for display (e.g., on a continuous, periodic, or on-demandbasis).

This document also provides a method for measuring blood flow through ablood pump in a subject. The method can include detecting leftventricular pressure via a sensor present at an inflow conduit of theblood pump, detecting arterial pressure via a sensor present at anoutflow conduit of the blood pump, and calculating blood flow based onthe difference between the left ventricular pressure and the arterialpressure. Thus, a blood flow calculation can be based on the pressuredrop across the pump, as well as on motor speed. Information regardingblood flow can be output for display. Left ventricular and arterialpressures can be detected on a continuous, periodic, or on-demand basis.In addition, the method can include retrieving stored informationregarding pressure changes within the blood pump.

Before such a blood pump is placed into the subject, it may be used indetermining a constant for use in calculating the blood flow. Forexample, a technician can measure the flow rate across the pump todetermine the pressure drop, and can derive a constant based on theparticular configuration of the pump. The pump can be calibrated todetermine the coefficient (multiplier) that can be used in calculationof blood flow after the blood pump has been connected to the subject andthe pump system is in use. Blood pump flow can be calculated by thecontroller using the following equation:

Flow=(pump outlet pressure−pump inlet pressure)×C, where C=anempirically derived constant describing the pump geometry, surfaceconditions, and viscosity.

In some cases, flow can be determined by using a “look up table” of flowas a function of the pressure drop across the pump, in combination withmotor speed.

OTHER EMBODIMENTS

It is to be understood that while the invention has been described inconjunction with the detailed description thereof, the foregoingdescription is intended to illustrate and not limit the scope of theinvention, which is defined by the scope of the appended claims. Forexample, the blood pump may be a rotary pump, a centrifugal blood pump,or any other type of blood pump.

Additionally, a blood pump controller (e.g., controller 80) can beimplanted or used externally in association with any of thecomputer-implemented methods described previously, according to oneimplementation. Controller 80 may include various forms of digitalcomputers, such as microcontrollers, customized application-specificintegrated circuits (ASICs), programmable logic controllers (PLCs),distributed control systems (DCSs), remote terminal units (RTUs),laptops, and any other appropriate computers.

A controller such as controller 80 can include, for example, aprocessor, a memory, a storage device, and an input/output device. Eachof the components can be interconnected using a system bus. Theprocessor can be capable of processing instructions for execution withinthe controller. The processor may be designed using any of a number ofarchitectures. For example, the processor may be a CISC (ComplexInstruction Set Computers) processor, a RISC (Reduced Instruction SetComputer) processor, or a MISC (Minimal Instruction Set Computer)processor.

In some embodiments, a processor can be a single-threaded processor. Insome embodiments, a processor can be a multi-threaded processor. Aprocessor can be capable of processing instructions stored in the memoryor on a storage device to display graphical information for a userinterface on an input/output device.

The memory can store information within controller 80. In someembodiments, the memory can be a computer-readable medium. In somecases, the memory can be a volatile memory unit. In other cases, thememory can be a non-volatile memory unit.

A storage device can be capable of providing mass storage for controller80. In some embodiments, a storage device can be a computer-readablemedium. In various cases, a storage device can be a hard disk device oran optical disk device.

An input/output device can provide input/output operations forcontroller 80. In some embodiments, an input/output device can include adisplay unit for displaying graphical user interfaces. The display mayhave a touch screen interface for receiving input from a user.Additionally, a input/output device can include buttons, dials, and/orswitches on the controller for receiving information from a user.

The features described can be implemented in digital electroniccircuitry, or in computer hardware, firmware, software, or incombinations thereof. The apparatus can be implemented in a computerprogram product tangibly embodied in an information carrier, e.g., in amachine-readable storage device for execution by a programmableprocessor; and method steps can be performed by a programmable processorexecuting a program of instructions to perform functions of thedescribed implementations by operating on input data and generatingoutput. The described features can be implemented advantageously in oneor more computer programs that are executable on a programmable systemincluding at least one programmable processor coupled to receive dataand instructions from, and to transmit data and instructions to, a datastorage system, at least one input device, and at least one outputdevice. A computer program is a set of instructions that can be used,directly or indirectly, in a computer to perform a certain activity orbring about a certain result. A computer program can be written in anyform of programming language, including compiled or interpretedlanguages, and it can be deployed in any form, including as astand-alone program or as a module, component, subroutine, or other unitsuitable for use in a computing environment.

Suitable processors for the execution of a program of instructionsinclude, by way of example and not limitation, both general and specialpurpose microprocessors, and the sole processor or one of multipleprocessors of any kind of computer. Generally, a processor can receiveinstructions and data from a read-only memory or a random access memory,or both. The essential elements of a computer are a processor forexecuting instructions and one or more memories for storing instructionsand data. A computer typically also will include, or be operativelycoupled to communicate with, one or more mass storage devices forstoring data files. Examples of such devices include magnetic disks,such as internal hard disks and removable disks magneto-optical disks,and optical disks. Storage devices suitable for tangibly embodyingcomputer program instructions and data include all forms of non-volatilememory, including, by way of example, semiconductor memory devices(e.g., EPROM, EEPROM, and flash memory devices), magnetic disks such asinternal hard disks and removable disks, and magneto-optical disks. Theprocessor and the memory can be supplemented by, or incorporated in,ASICs.

To provide for interaction with a user, the features can be implementedon a computer having a display device such as a liquid crystal display(LCD) monitor for displaying information to the user.

It also is understood that while the invention described herein is of ablood pump to aid the left ventricle, other embodiments also arecontemplated. For example, a blood pump with pressure transducers on theinlet and/or the outlet can be used to supplement flow from the rightventricle. The inlet conduit can be attached to the right atrium or thevena cava, which would indicate central venous pressure while the pumpoutlet conduit can be attached to the pulmonary artery (PA) to indicatePA pressure. In such embodiments, blood from the venous return can bepushed through the lungs to the left ventricle.

In some embodiments, one pump can be used on the right side and anotherpump can be used on the left side, thereby creating a total artificialheart or bilateral system. Total blood flow can be controlled by properadjustment of the pressure levels at each pump. In some embodiments, thecontroller can be implanted in the patient with data transmission via apercutaneous lead, or with wireless transmission via an electricalsignal.

Other aspects, advantages, and modifications are within the scope of thefollowing claims.

What is claimed is:
 1. A blood pump system, comprising: a blood pumpincluding an inflow conduit for receiving blood from a ventricle of apatient and an outflow conduit for returning blood to an artery of thepatient; a sensor configured to generate an inflow conduit pressuresignal indicative of a pressure of blood within the inflow conduit; anda controller operatively connected to the blood pump and the sensor, thecontroller being configured to control a speed of the blood pump basedon changes in the pressure of blood within the inflow conduit generatedby the heart, wherein the speed of the blood pump is decreased inresponse to an increase in the pressure of blood within the inflowconduit generated by the ventricle.
 2. A blood pump system, comprising:a blood pump including an inflow conduit for receiving blood from aventricle of a patient and an outflow conduit for returning the blood toan artery of the patient; a controller operatively connected to theblood pump and configured to: control the speed of the blood pump over afirst period of time encompassing multiple contractions of the ventricleto provide circulatory support to the patient to maintain a positivelevel of systolic blood pressure within the ventricle within a firstpredetermined range; subsequent to the first period of time, control thespeed of the blood pump over a second period of time encompassingmultiple contractions of the ventricle to provide a reduced level ofcirculatory support to the patient relative to the circulatory supportprovided to the patient over the first period of time; subsequent to thesecond period of time, control the speed of the blood pump over a thirdperiod of time encompassing multiple contractions of the ventricle toprovide circulatory support to the patient to maintain a positive levelof systolic blood pressure within the ventricle within the firstpredetermined range; and determine whether the ventricle providedcirculatory support to the patient over the second period of time thatexceeded a predetermined minimum level of circulatory support.
 3. Theblood pump system of claim 2, wherein: the ventricle is a left ventricleof the patient; and the first predetermined range is between an aorticblood pressure of the patient and about 20 mm Hg below the aortic bloodpressure.
 4. The blood pump system of claim 2, wherein: the ventricle isa right ventricle of the patient; and the first predetermined range isbetween 5 mm Hg and 20 mm Hg.
 5. The blood pump system of claim 2,wherein the controller is configured to: control the speed to pump bloodwithin a first predetermined range of flow rates to provide circulatorysupport to the patient over the first period of time; control the speedto pump blood at a reduced flow rate over the second period of timerelative to the flow rate over the first period of time; and control thespeed to pump blood within the first predetermined range of flow ratesto provide circulatory support to the patient over the third period oftime.
 6. The blood pump system of claim 5, wherein the reduced flow rateis between about 0.5 liters/minute and 1.5 liters/minute less than aflow rate during the first period of time.
 7. The blood pump system ofclaim 2, wherein the reduced level of circulatory support results insystolic blood pressure within the ventricle being maintained at aboutan arterial blood pressure within the artery.
 8. The blood pump systemof claim 2, wherein the first period of time is at least 5 minutes. 9.The blood pump system of claim 2, wherein the second period of time isbetween 1 and 5 minutes.
 10. The blood pump system of claim 2, wherein:the ventricle is a left ventricle of the patient; the artery is an aortaof the patient; and the controller is configured to control the speed ofthe blood pump to revert from providing the reduced level of circulatorysupport to the patient to providing circulatory support to the patientto maintain a positive level of systolic blood pressure within theventricle within the first predetermined range in response to detectingat least one of: a decrease in aortic blood pressure of at least a firstpredetermined amount during the second period of time, and an increaseof an end diastolic blood pressure within the left ventricle of at leasta second predetermined amount during the second period of time.
 11. Theblood pump system of claim 2, wherein: the ventricle is a rightventricle of the patient; the artery is a pulmonary artery of thepatient; and the controller is configured to control the speed of theblood pump to revert from providing the reduced level of circulatorysupport to the patient to providing circulatory support to the patientto maintain a positive level of systolic blood pressure within theventricle within the first predetermined range in response to detectingat least one of: a decrease in pulmonary artery blood pressure of atleast a first predetermined amount during the second period of time, andan increase of an end diastolic blood pressure within the rightventricle of at least a second predetermined amount during the secondperiod of time.
 12. The blood pump system of claim 2, wherein thecontroller is configured to determine whether the ventricle providedcirculatory support to the patient over the second period of time thatexceeded the predetermined minimum level of circulatory support bydetermining whether a decrease in blood pressure in the artery of atleast a first predetermined amount occurs during the second period oftime.
 13. The blood pump system of claim 12, wherein the controller isconfigured to determine whether the ventricle provided circulatorysupport to the patient over the second period of time that exceeded thepredetermined minimum level of circulatory support by determiningwhether an increase of an end diastolic blood pressure within theventricle of at least a second predetermined amount occurs during thesecond period of time.
 14. The blood pump system of claim 2, wherein thecontroller is configured to: in response to determining that theventricle provided circulatory support to the patient over the secondperiod of time that exceeded the predetermined minimum level ofcirculatory support, subsequent to the third period of time, control thespeed of the blood pump over a fourth period of time encompassingmultiple contractions of the ventricle to provide a reduced level ofcirculatory support to the patient relative to the circulatory supportprovided to the patient over the third period of time, the fourth periodof time being greater than the second period of time; subsequent to thefourth period of time, control the speed of the blood pump over a fifthperiod of time encompassing multiple contractions of the ventricle toprovide circulatory support to the patient to maintain a positive levelof systolic blood pressure within the ventricle within the firstpredetermined range; and determine whether the ventricle providedcirculatory support to the patient over the fourth period of time thatexceeded the predetermined minimum level of circulatory support.
 15. Theblood pump system of claim 14, wherein the controller is configured to:in response to determining that the ventricle provided circulatorysupport to the patient over the fourth period of time that exceeded thepredetermined minimum level of circulatory support, subsequent to thefifth period of time, control the speed of the blood pump over a sixthperiod of time encompassing multiple contractions of the ventricle toprovide a reduced level of circulatory support to the patient relativeto the circulatory support provided to the patient over the fifth periodof time, the sixth period of time being greater than the fourth periodof time; subsequent to the sixth period of time, control the speed ofthe blood pump over a seventh period of time encompassing multiplecontractions of the ventricle to provide circulatory support to thepatient to maintain a positive level of systolic blood pressure withinthe ventricle within the first predetermined range; and determinewhether the ventricle provided circulatory support to the patient overthe sixth period of time that exceeded the predetermined minimum levelof circulatory support.
 16. A blood pump system, comprising: a bloodpump including an inflow conduit for receiving blood from a ventricle ofa patient and an outflow conduit for returning blood to an artery of thepatient; a sensor configured to generate an inflow conduit pressuresignal indicative of a pressure of blood within the inflow conduit; anda controller operatively connected to the blood pump and the sensor, thecontroller being configured to control a speed of the blood pump basedon the inflow conduit pressure signal to: maintain the pressure of bloodwithin the inflow conduit equal to or greater than a lower threshold foravoiding ventricular collapse, and maintain the pressure of blood withinthe inflow conduit equal to or less than an upper threshold to maintainan end diastolic blood pressure within an acceptable range.
 17. Theblood pump system of claim 16, wherein: the ventricle is a leftventricle; the lower threshold is within a range from 10 mm Hg to 40 mmHg; and the upper threshold is within a range from 65 mm Hg to about ablood pressure within an aorta of the patient.
 18. The blood pump systemof claim 16, wherein: the ventricle is a right ventricle; the lowerthreshold within a range from 5 mm Hg to 20 mm Hg; and the upperthreshold is within a range from 20 mm Hg to about 60 mm Hg.